Peroxiredoxin Overexpression in MCF-7 Breast Cancer Cells and Regulation by Cell Proliferation and Oxidative Stress

Androgens inhibit the growth of breast cancer cells in vitro and in vivo by mechanisms that remain poorly defined. In this study, treatment of asynchronously growing MCF-7 breast cancer cells with the androgen, 5alpha-dihydrotestosterone (DHT), was shown to inhibit cell proliferation and induce moderate increases in the proportion of G1 phase cells. Consistent with targeting the G1-S phase transition, DHT pretreatment of MCF-7 cultures impeded the serum-induced progression of G1-arrested cells into S phase and reduced the kinase activities of cyclin-dependent kinase (Cdk)4 and Cdk2 to less than 50% of controls within 3 days. DHT treatment was associated with greater than twofold increases in the levels of the Cdk inhibitor, p27(Kip1), while p21(Cip1/Waf1) protein levels remained unchanged. During the first 24 h of DHT treatment, levels of Cdk4-associated p21(Cip1/Waf1) and p27(Kip1) were reduced coinciding with decreased levels of Cdk4-associated cyclin D3. In contrast, DHT treatment caused increased accumulation of Cdk2-associated p21(Cip1/Waf1), with no significant alterations in levels of p27(Kip1) bound to Cdk2 complexes. These findings suggest that DHT reverses the Cdk4-mediated titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and that the increased association of p21(Cip1/Waf1) with Cdk2 complexes in part mediates the androgen-induced growth inhibition of breast cancer cells.

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Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Biomolecules ◽

10.3390/biom11050743 ◽

2021 ◽

Vol 11 (5) ◽

pp. 743

Author(s):

Oluwaseun Akinyele ◽

Heather M. Wallace

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cells ◽

Growth Responses ◽

Cancer Management ◽

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Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.

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Oxidative Stress in Caffeine Action on the Proliferation and Death of Human Breast Cancer Cells MCF-7 and MDA-MB-231

Nutrition and Cancer ◽

10.1080/01635581.2020.1795693 ◽

2020 ◽

pp. 1-11

Author(s):

Kaliana Larissa Machado ◽

Poliana Camila Marinello ◽

Thamara Nishida Xavier Silva ◽

Cássio Fernando Nunes Silva ◽

Rodrigo Cabral Luiz ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mcf 7

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Mango Fruit Extracts Differentially Affect Proliferation and Intracellular Calcium Signalling in MCF-7 Human Breast Cancer Cells

Journal of Chemistry ◽

10.1155/2015/613268 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Meng-Wong Taing ◽

Jean-Thomas Pierson ◽

Paul N. Shaw ◽

Ralf G. Dietzgen ◽

Sarah J. Roberts-Thomson ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Intracellular Calcium ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Cultivar Differences ◽

Human Breast Cancer Cells ◽

Human Breast ◽

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The assessment of human cancer cell proliferation is a common approach in identifying plant extracts that have potential bioactive effects. In this study, we tested the hypothesis that methanolic extracts of peel and flesh from three archetypal mango cultivars, Irwin (IW), Nam Doc Mai (NDM), and Kensington Pride (KP), differentially affect proliferation, extracellular signal-regulated kinase (ERK) activity, and intracellular calcium ([Ca2+]I) signalling in MCF-7 human breast cancer cells. Mango flesh extracts from all three cultivars did not inhibit cell growth, and of the peel extracts only NDM reduced MCF-7 cell proliferation. Mango cultivar peel and flesh extracts did not significantly change ERK phosphorylation compared to controls; however, some reduced relative maximal peak[Ca2+]Iafter adenosine triphosphate stimulation, with NDM peel extract having the greatest effect among the treatments. Our results identify mango interfruit and intrafruit (peel and flesh) extract variability in antiproliferative effects and[Ca2+]Isignalling in MCF-7 breast cancer cells and highlight that parts of the fruit (such as peel and flesh) and cultivar differences are important factors to consider when assessing potential chemopreventive bioactive compounds in plants extracts.

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Abstract 496: Adaptive response to chronic oxidative stress involves epithelial-mesenchymal transition in MCF-7 breast cancer cells

10.1158/1538-7445.am2014-496 ◽

2014 ◽

Author(s):

Prathap Kumar S. Mahalingaiah ◽

Logeswari Ponnusamy ◽

Kamaleshwar P. Singh

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cancer Cells ◽

Adaptive Response ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Chronic Oxidative Stress ◽

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GPR91 Receptor Mediates Protection against Doxorubicin-Induced Cardiotoxicity without Altering Its Anticancer Efficacy. An In Vitro Study on H9C2 Cardiomyoblasts and Breast Cancer-Derived MCF-7 Cells

Cells ◽

10.3390/cells9102177 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2177

Author(s):

Matthieu Dallons ◽

Esma Alpan ◽

Corentin Schepkens ◽

Vanessa Tagliatti ◽

Jean-Marie Colet

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Protective Effect ◽

Cancer Cells ◽

1H Nmr ◽

Breast Cancer Cells ◽

Extracellular Fluid ◽

H9c2 Cells ◽

Experimental Conditions ◽

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Doxorubicin (DOX) is an anticancer drug widely used in oncology, especially for breast cancer. The main limitation of DOX treatment is its cardiotoxicity due to the cumulative dose. Clinically, DOX-induced cardiomyopathy develops as a progressive heart failure caused by a progressive cardiomyocyte’s death. For long, the oxidative stress induced by DOX was considered as the main toxic mechanism responsible for heart damage, but it is now controverted, and other processes are investigated to develop cardioprotective strategies. Previously, we studied DOX-induced cardiotoxicity and dexrazoxane (DEX), the only cardioprotective compound authorized by the FDA, by 1H-NMR metabonomics in H9C2 cells. We observed an increased succinate secretion in the extracellular fluid of DEX-exposed cardiomyocytes, a finding that led us to the hypothesis of a possible protective role of this agonist of the GPR91 receptor. The objective of the present work was to study the effect of succinate (SUC) and cis-epoxysuccinate (cis-ES), two agonists of the GPR91 receptor, on DOX-induced cardiotoxicity to H9C2 cells. To this purpose, several toxicity parameters, including cell viability, oxidative stress and apoptosis, as well as the GPR91 expression, were measured to assess the effects of DEX, SUC and cis-ES either alone or in combination with DOX in H9C2 cells. A 1H-NMR-based metabonomic study was carried out on cellular fluids collected after 24 h to highlight the metabolic changes induced by those protective compounds. Moreover, the effects of each agonist given either alone or in combination with DOX were evaluated on MCF-7 breast cancer cells. GPR91 expression was confirmed in H9C2 cells, while no expression was found in MCF-7 cells. Under such experimental conditions, both SUC and cis-ES decreased partially the cellular mortality, the oxidative stress and the apoptosis induced by DOX. The SUC protective effect was similar to the DEX effect, but the protective effect of cis-ES was higher on oxidative stress and apoptosis. In addition, the metabonomics findings pointed out several metabolic pathways involved in the cardioprotective effects of both GPR91 agonists: the stimulation of aerobic metabolism with glucose as the main fuel, redox balance and phospholipids synthesis. Finally, none of the GPR91 agonists jeopardized the pharmacological effects of DOX on MCF-7 breast cancer cells.

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